Engineered biomimetic nanoparticles achieve targeted delivery and efficient metabolism-based synergistic therapy against glioblastoma

Abstract Glioblastoma multiforme (GBM) is an aggressive brain cancer with a poor prognosis and few treatment options. Here, building on the observation of elevated lactate (LA) in resected GBM, we develop biomimetic therapeutic nanoparticles (NPs) that deliver agents for LA metabolism-based synergis...

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Published inNature communications Vol. 13; no. 1; p. 4214
Main Authors Lu, Guihong, Wang, Xiaojun, Li, Feng, Wang, Shuang, Zhao, Jiawei, Wang, Jinyi, Liu, Jing, Lyu, Chengliang, Ye, Peng, Tan, Hui, Li, Weiping, Ma, Guanghui, Wei, Wei
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group 21.07.2022
Nature Publishing Group UK
Nature Portfolio
Subjects
Biomimetics
Blood-brain barrier
Brain cancer
Brain tumors
Cancer
Cell culture
Cell cycle
Cytotoxicity
Encapsulation
Glioblastoma
Glioma cells
Histones
Hydrogen peroxide
Lactate oxidase
Lactic acid
Membranes
Metabolism
Nanoparticles
Oxalic acid
Patients
Pyruvic acid
Self-assembly
Singlet oxygen
Synergism
Therapy
Toxicity
Xenografts
Xenotransplantation
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Summary:Abstract Glioblastoma multiforme (GBM) is an aggressive brain cancer with a poor prognosis and few treatment options. Here, building on the observation of elevated lactate (LA) in resected GBM, we develop biomimetic therapeutic nanoparticles (NPs) that deliver agents for LA metabolism-based synergistic therapy. Because our self-assembling NPs are encapsulated in membranes derived from glioma cells, they readily penetrate the blood-brain barrier and target GBM through homotypic recognition. After reaching the tumors, lactate oxidase in the NPs converts LA into pyruvic acid (PA) and hydrogen peroxide (H 2 O 2 ). The PA inhibits cancer cell growth by blocking histones expression and inducing cell-cycle arrest. In parallel, the H 2 O 2 reacts with the delivered bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate to release energy, which is used by the co-delivered photosensitizer chlorin e6 for the generation of cytotoxic singlet oxygen to kill glioma cells. Such a synergism ensures strong therapeutic effects against both glioma cell-line derived and patient-derived xenograft models.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-31799-y